Researchers examined whether lower than normal T levels in elderly men were associated with a reduced quality of life (QoL), as well as physical and mental health, and whether T treatment could improve these conditions.

Unlike earlier testosterone treatment studies that recruited by advertising or direct mailing, researchers contacted elderly men (aged 60–80 years old) surveyed as part of the fifth (2001) Tromsø survey that measured T in 3,447 men. Sixty-nine elderly men with low T (defined as ≤11.0 nmol/l) and 104 men with normal T (>11.0 nmol/l) (control group) took part in a nested case-control study. Of the 69 men with low T, 31were excluded from participation in the one year intervention study due mainly to PSA levels above the reference range (>4.0µg/l) (no.18) or the use of warfarin (no.6). As a result 19 men were included in each of the T and placebo treatment groups (randomized in a double-blind fashion) – one man later withdrew from each group and one man from the T group died from cardiac arrhythmia not considered to be related to T therapy. Treatment was by an intramuscular injection of testosterone undecanoate 1000mg (Nebido®) or an identical looking placebo administered by a nurse (ensuring 100 per cent compliance) at baseline and again at six, 16, 28, and 40 weeks. After 52 weeks the initial examinations and tests were repeated.

Key Points

The nested case-control study showed:

No difference in Fat Free Mass (FFM) beween the two groups (low and normal T), but Fat Mass (FM) percentage was significantly higher in the low T group (32.2% vs 25.9%; P<0.001) compared with controls – this group also had higher weight, waist circumference, and total abdominal adipose tissue (TAT)

Muscle strength was similar between the groups, but the control group performed significantly better in two of the three functional tests. Bone Mineral Density (BMD) measured in both the lumbar spine and hip showed no significant difference between the groups

At the Oral Glucose Tolerance Test men with low T had significantly higher fasting and two hour glucose levels compared with the control group. Likewise, the HbA1c, insulin, C-peptide and triglycerides levels and insulin resistance (HOMA) values were significantly higher in men with subnormal testosterone levels

Men in the control group reported better overall and somatic Quality of Life (QoL) scores (AMS) although the scores in the sexual domain were not significantly different. In the Beck Depression Inventory the control group reported a significantly better total and second subscale score

There were no differences between groups in the General Health Questionnaire or World Health Organisation quality of life old score (WHOQOL-OLD)

The intervention study showed that:

Total and free T increased significantly in the T group. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) decreased in the T group and at the end of the study were significantly lower in the T group compared with placebo

FFM increased and FM reduced significantly during T treatment compared to the placebo group at the end of the study (FFM: +4.2 kg in T group, +0.4 kg in placebo;
FM: -5.3kg in T group, -0.6 kg in placebo) while weight, BMI and waist circumference did not change significantly

BMD in the hip increased significantly in the T group and there was a significant difference between the groups at the end of the study

T did not increase strength in knee extension or handgrip strength, but in the placebo group handgrip strength was reduced in both the dominant and non-dominant hand such that at the end of the study there were significant differences between the groups

There was no significant difference in QoL, cognitive function or emotional function between the groups at the end of the study

Serum PSA, hematocrit and hemoglobin increased in the T group and by the end of the study were significantly higher than in the placebo group; two men in the T group (and one in the placebo group) had PSA levels >4.0µg/l by the end of the study

What is known

Testosterone levels decrease with age2, 3, 4, 5 but this is characterised by high inter-individual variability.3

Some age-related changes in muscle and fat mass, bone mineral density (BMD) and sexual and cognitive functions resemble those observed in young testosterone deficient men. Such parallels suggest that T treatment in partially androgen-deficient older men may prevent or reverse these changes. However, placebo-controlled trials in older men with low or subnormal testosterone levels have so far yielded inconsistent results.6

In earlier studies T has been associated with a greater improvement in grip compared with placebo, although no earlier study has reported T making a difference to lower extremity muscle strength.7, 8, 9, 10

What this study adds

The main findings were that older men with low T had an unfavourable metabolic profile and that T treatment mainly improved body composition (reducing FM, SAT, TAT and increasing FFM) without affecting body weight. T treatment had no effect on the glucose metabolism or the lipids.

Men receiving T treatment did have significantly better grip than the placebo group at the end of the study as grip strength in the placebo group reduced - T maintained muscle strength in this limb.

This study is in line with other studies that have not shown an increase in strength in knee extension following T.

BMD in the hip increased significantly during T and there was a significant difference between the groups at the end of the treatment.